1. Retinoic acid-induced protein 14 links mechanical forces to Hippo signaling.
- Author
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Jeong, Wonyoung, Kwon, Hyeryun, Park, Sang Ki, Lee, In-Seob, and Jho, Eek-hoon
- Abstract
Cells sense and respond to various mechanical forces from the extracellular matrix primarily by modulating the actin cytoskeleton. Mechanical forces can be translated into biochemical signals in a process called mechanotransduction. Yes-associated protein (YAP) is an effector of Hippo signaling and a mediator of mechanotransduction, but how mechanical forces regulate Hippo signaling is still an open question. We propose that retinoic acid-induced protein 14 (RAI14) responds to mechanical forces and regulates Hippo signaling. RAI14 positively regulates the activity of YAP. RAI14 interacts with NF2, a key component of the Hippo pathway, and the interaction occurs on filamentous actin. When mechanical forces are kept low in cells, NF2 dissociates from RAI14 and filamentous actin, resulting in increased interactions with LATS1 and activation of the Hippo pathway. Clinical data show that tissue stiffness and expression of RAI14 and YAP are upregulated in tumor tissues and that RAI14 is strongly associated with adverse outcome in patients with gastric cancer. Our data suggest that RAI14 links mechanotransduction with Hippo signaling and mediates Hippo-related biological functions such as cancer progression. Synopsis: Cells sense and respond to mechanical forces primarily by modulating the actin cytoskeleton. Retinoic acid-induced protein 14 (RAI14) is responsive to extracellular mechanical forces, thereby regulating cell proliferation by modulating the Hippo signaling pathway. The positive regulation of YAP/TAZ activity by RAI14 is mainly mediated through NF2. Interactions between RAI14, NF2, and LATS, in response to ECM stiffness and F-actin integrity, regulate YAP/TAZ activity. RAI14 promotes cell proliferation in a Hippo signaling-dependent manner. The RAI14-Hippo signaling axis plays a pivotal role in gastric cancer progression. Cells sense and respond to mechanical forces primarily by modulating the actin cytoskeleton. Retinoic acid-induced protein 14 (RAI14) is responsive to extracellular mechanical forces, thereby regulating cell proliferation by modulating the Hippo signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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